J. Org. C h e m .
1137
1988,53, 1137-1140
was performed on Merck silica gel 60 (type9385). Petroleum ether refers to the fraction of bp 50-60 OC. 2-Hydroxy-5,l0,15,20-tetraphenylporphyrin(2). 2-(Benzoyloxy)-5,10,15,20-tetraphenylporphyrin4 (3) (240mg, 0.33 "01) was dissolved in tetrahydrofuran (6 mL) and ethanol (6 mL), protected from light, and heated to boiling. A saturated solution of sodium hydroxide in ethanol (2mL) was added, and the solution wa8 boiled under nitrogen for 45 min. The mixture was diluted with water and the product extracted into chloroform. The combined extracts were dried (Na2S04),and the solvent was removed under reduced pressure to give a purple solid. Light was rigorously excluded in all workup procedures. Minor impurities were removed by flash chromatography on silica gel. The major band was eluted with CHzClzand evaporated, and the product was washed successively with hot methanol and pentane to give 2 as purple crystals (170mg, 83%): >300 "C; visible spectrum A, 419 (log c 5.39),517 (4.15),556 (3.85),592 (3.77), 648 nm (3.76);'H NMR (CD2C12)6 enol -2.94 (br s, NH), 1.53 (br s, OH), 8.62 and 8.85 (b AB q, JAB= 5.03 Hz,H17,18),8.82 and 8.87 (b AB q, JAB= 5.00 Hz, H7,J, 8.83 (br s, H12,13), keto -2.00, -2.06 (2br s, NH), 4.62 (8, CH2),8.49 and 8.72 (b AB q, JAB = 5.10 Hz, H1,,18), 8.53 and 8.78 (b AB 9, JAB= 5.10 Hz, H7&, 8.54 and 8.58 (AB q, J = 4.50 Hz, HIZIJ, 7.65-7.80 (m, H&, 7.87-8.25 (m, Ho); mass spectrum, m / z 630 (M', 100). The deuteriated derivative was prepared by three successive equilibrations of a solution of the porphyrin 2 in toluene-d8with DzO. The solution was dried over NazS04prior to NMR analysis. 2-Amino-5,10,15,20-tetraphenylporphyrin(4). The crude aminoporphyrin 4 was prepared by the method of Baldwin et al.6 Purification was effected by chromatography over silica gel (dichloromethane/petroleumether, 1:l)with careful exclusion of light. The major brown band was collected and the solvent removed under reduced pressure. The residue was boiled in methanol and filtered to give 4 as shiny fine purple crystals (30
mg, 64%): mp >300 "C; 'H NMR (CD2C12)6 -2.78 (br s, NH), 4.52 (br s, NH2),7.70-7.86 (m, H,,), 8.11-8.22 (m, Ho),8.74 and 8.52 (ABq,JAB= 4.70 Hz, H1,,18), 8.78 and 8.69 (AB q,JAB = 4.79 Hz, H7,8), 8.79 and 8.81 (AB9, JAB = 4.60 Hz, H12,13). (2-Hydroxy-5,10,15~0-tetraphenylporphinato)~nc(II) (5). Treatment of 2 with zinc(I1) acetate according to the method of Fuhrhop and Smith' gave the metalated porphyrin' 5 in quantitative yield visible spectrum A, 424 (log e 5.45),552 (4.151, 588 (3.70),618 nm (3.34);'H NMR (CDCl,) 6 5.95 (s, OH), 7.69-7.92 (m, Hm,,), 8.09 (s, H3),8.15-8.25 (m, Ho),8.65 and 8.90 (AB q, JAB = 4.65 Hz, H1,,18), 8.88 and 8.94 (AB q, JAB = 4.71 Hz, He&,8.91 and 8.92 (AB q, JAB= 4.66 Hz, H12,13);mass spectrum, m/z 692 (M', %h,loo),694 (M', =Zn, 70),696 (M', *Zn,45). (2-Hydroxy-5,10,15f0-tetraphenylporphinato)cop~r(II) (6). Porphyrin 2 (100mg, 0.16 "01) was treated with copper(1I) acetate according to the method of Fuhrhop and Smith.' The crude metalated porphyrin was chromatographed on silica gel (dichloromethane/petroleumether, 1:l). The major red band was collected, and the solvent was removed under reduced pressure. Recrystallization of the resultant product from dichloromethane/pentane afforded pure 6 as fine purple crystals (86 mg, 78%): mp >300 "C; visible spectrum A, 416 (log e 5.62),539 (4.28),5.79 (3.83),601 nm (3.37);mass spectrum, m / z 691 (M+, loo),675 (6). Anal. Calcd for CUHz8N40Cu: C, 76.34;H, 4.08; N, 8.10. Found: C, 75.62;H, 4.00;N, 8.10.
Acknowledgment. This research was supported by a grant from the Australian Research Grants Scheme (to M.J.C.) and a n Australian Government Postgraduate Scholarship (to M.M.H.). Rsgistry No. 2a, 102305-84-0;2b, 102305-84-0;2d, 112374-51-3; 3, 102305-83-9;4, 82945-59-3; 5, 54329-80-5; 6,95386-85-9.
Polarizability Effects on the Aqueous Solution Basicity of Substituted Pyridines Jose-Luis M. Abboud,' Javier Catalin,** Jose Elguero,l and Robert W. Taft*l Departamento de Qu@ca, Universidad Autdnoma de Madrid, E-28049 Madrid, Spain, Znstitutos de Qulmica Fisica Rocasolano' y Quimica Msdica, C.S.Z.C.,E-28006 Madrid, Spain, Department of Chemistry, University of California, Zrvine, Zrvine, California 92717 Received October 19,1987
A quantitative dissection of polarizability (P),field (F)and resonance ( R ) substituent contributions to the relative gas-phase and aqueous solution basicities of 2-,3-,and 4-substituted pyridines (XPy) is described in thiswork. The standard-freeenergy changesfor the reaction XPyH' + Py F'C XPy + PyH+ (eq 1)in the gas-phase (6AG"J and in aqueous solution (6AGa,,,) have been analyzed. 6AGo4 has been found to be the sum of F, R, and P while 6AGO only depends on F and R. &AGO, corrected for polaruability, @AGO, - P)is a linear function of &AGO,. This rgationship holds for substituents in any of the three positions (ortho, meta, para), including 2-mono- and 2,6-disubstituted pyridines. These results show that the fundamental differences between gas-phase and solution basicities of pyridine are (i) the essentially complete disappearanceof polarizability effects in solution and (ii) an attenuation (by a factor of ca. 2.3) of field and resonance contributions.
Studies of gas-phase acidities and basicities of organic compounds have led Taft and Topsoml to the quantitative dissection of substituent polarizability (uJ, field-inductive (q), and resonance (qJeffects. This scheme has successfully been applied to the analysis of structural effects on many kinds of proton-transfer reactions in the gas phase. A preliminary assessment also showed the applicability of this treatment to solution reactions wherein t Instituto
+
"Rocasolano".
* Universidad AuJ6noma.
substituent solvation effects are absent or are corrected for. Here, we wish to report that this formalism has also allowed the analysis of the main factor governing the basicity of 2-, 3-, and 4-substituted pyridines in aqueous solution. Consider the proton-exchange reaction 1, where P y stands for pyridine itself and X-Py is a 2-, 3-, or 4-substituted pyridine. The standard free-energy changes for X-PyH' P y F? X-Py + PyH+ (1)
5 Instituto
de Quimica MBdica. University of California.
(1) Taft, R. W.;Topsom, R. D.h o g . Phys. Org. Chem. 1987, 16, 1.
0022-3263/88/1953-1137$01.50/00 1988 American Chemical Society
1138 J. Org. Chem., Vol. 53,No.6, 1988
Abboud et al.
Table I. Thermodynamic D a t a for Reaction I at 25 "C in the Gas-Phase a n d in Aqueous Solution SAG',: 6AG', - P.d SAG' subst 2-NMe, 2-n-C8H,, 2-t-Bu 2-i-Pr 2-NH2 2-Et 2-Me 2-SMe 2-OMe none 2x1 2-F 2-CN 2,6-t-Bu2 2,6-i-Pr 2,6-Me2 2,4-t-Bu2 3-NMe, 3-Et 3-OMe 3-Me 3-NH2 3-C02Me 3-MeCO 3-CI 3-F 3-CF3 3-CN 3-NOZ 4-NMe 4-NH, 4-OMe 4-t-Bu 4SMe 4-Et 4-Me 4-CHCH2 4-C02Me 4-Cl 4-MeCO 4CFs 4CN 4N02
kcalmol-'
kcalmol-'
.Me*
kcal"%
~~
8.8 6.9'
6.6 6.4 4.8 4.5 3.8 1.6
0.6 0.0 -6.6 -10.2 -13.2 10.9 9.1' 6.7 10.5( 9.5 3.1 3.0 2.9 0.2 -2.8 -3.9 -6.2
-7.0 -8.6 -12.0 -13.5 15.6 11.4 7.1 5.7 5.4 4.2 3.5 2.4 -2.3 -3.4 -3.7 -8.3 -11.1 -12.6
6.0 3.1 1.8 3.3 3.8 1.4 1.6 -2.8 4.5 0.0 -9.5 -9.4 -16.1 1.3 1.2 2.2 2.1
7.7 1.0 2.3 1.4 4.5 -4.9 -6.2 -8.0 -6.5 -9.7 -13.9 -14.6 13.5 10.6 6.3 2.1 2.1 1.8 1.8 0.0 -4.7 -5.5
2.4'
l.0d 0.7" 0.W 2.e 0.Y
l.v
-2.2' -2.9'
O P -6.1" -7.7" -7.50 -0.3' 1.4' 2.v 2.2' 1.7' 0.5' -0.6" 0.Y
cd
c',
1.lh
-2.9" -2.V -3.3" -3.0" -3.86 -5.3* *.Ob
-6.3 -9.5 -13.3 -13.8
6.V 5.3h 1.9"
Figure 1. SAG, va 6AG, for reaction 1: (0) ortho; ( 0 )meta, (0) para.
t
0.6' 1.V 1.1" i.ij
0.6' -2.4" -1.9-2.3"' -3.c -4.P -5.4h
'Unless stated otherwise, these data are taken from ref 1-3 and references cited therein. 'Reference 4. (Reference 5. dCalculated With P. and on values from ref 1. 'Reference 6a. f h f e r e n c e 6b. 'Reference 6c. hRefence 6d. ,Reference 6e. 'Reference 6f. 'Reference 6g. 'Reference 6h. "Reference 6i. "Reference 6j. 'Reference 6k. PReference 61. 'Reference 6m. 'Reference 6n.
10-
00-2.0-
this reaction in the gas phase and in solution, respectively, noted 6AGog and 6AG" are given in Table I. Figure 1,a plot of 6AG'$ w 6 A P 9 shows a crude linear relationship, a fact already noticed by Beauchamp,7 Taft,"
-10
F
(2) T&, R W. Prog. Phys. Org. Chem. 1983,14,247.
(3) Aue, D. H.; Bowers, M. T. In Gas-Phose Ion Chemistry; Bowers, M. T.. Ed.; Academic: New York, 1979; Vel. 2. (4) Meot-Ner, M.; Sieck, L. W. J. Am. Chem. Soe. 1983, 10.5, 2955. (5) Hopkins, H. P., Jr.; Jahagirdar, D. V.; Moulik, S.P.; Aue, D. H.; Webb, H. M.: Davidson. W.R.; Pedley, M. D.J. Am. Chem. SOC.1984, IM A?Al -I", (6) (a) Cru*ge, F; Giradt, G.; Canstal, S.;Laammbe, J.; Rumpf, P. Bull. SOC.Chim. Fr. 1970,3889. (b) Linnel, R. H.J. Org. Chem. 1960, 25,290. (e) Brown, H. C.; Mihm, X.R. J. Am. Chem. Soc. 1955,77,1723. (d) Bellobono, I. R.;Favini. G. J. Chem. Soe. 1971,2034. (e) Andon, R. J. L.; Cox, J. D.; Herington, E. F. G.Trans. Famdny Soe. 1954,50,918. (0Sacmni, L.;Paoletti, P.: Ciampolini, M. J. Am. Chem. Soe. 1960,82, 3831. (9) Albert, A.; Barlin, G. B. J. Chem. SOC.B 1959, 2384. (h) Mu", R.K.;Bmlo, F.J. Am. Chem. Soc. 1955,77,3484. (i) Fixher, A.: Galloway, W.J.; Vaughan, J. J. Chem. SOC.B 1964,3591. (i) Brown, H. C.;MeDaniel, D. H. J. Am. Chem. Soe. 1955,77,3752. (k) Mason, S. F. J. Chem. Soc. 1959,1247. 0)Cabani, S.;Conti, G. Gorr. Chim. Itol. 1965.95.533. (m) Amett, E. M.; Chawls, B.;Bell, L.; Taagepera, M.; Hehre,W.J.; Taft, R. W. J.Am. Chem. Soc. 1977,99,5729 and ref 7. (n) Pietrzyk, A.; Wiley, R.; McDaniel, D. H.J . Org. Chem. 1957, 22, 83.
0
.
I
-80
-cO
a0
1.
c
ta
80
Figure 2. SAG, - P vs 6AG, for reaction 1: (0) ortho; ( 0 )meta, ( 0 )para.
and Aue, Liotta, and HopkinsJb It has recently been shown' that the differential standard free-energy changes, (7) Taagepera, M.; Summerhays, K.D.; Hehre, W. J.; Topsom, R. D.; Proas, A.; Radom, L.; Taft, R.W . J. Org. Chem. 1981,46,891.
J. Org. Chem., Vol. 53,No. 6, 1988
Aqueous Solution Basicity of Substituted Pyridines
subst 2-X 3-X 4-X
Table 11. Quantitative Dissection"of the Experimental 8AGoSband Values AFa -pF(de -pa(ade -pdW AFF -pRk)' -pdaq)e
-pa($ 6.4 f 0.7 4.2 f 1.2 4.8 f 0.9
0.0 0.0 0.0
very large verylarge very large
27.0 f 1.8 22.8 f 1.2 21.5 f 1.1
14.3 f 2.0 9.1 f 1.0 8.2 f 0.6
1.9 2.5 2.6
14.3 f 1.8 16.3 f 1.5 25.9 f 1.2
7.0 f 2.1 5.1 f 1.0 12.0 f 0.7
1139
AFR 2.0
3.2 2.2
the data from Table I. 'All the p values are given with error limits of two standard deviations. The vu, uF, and 'Using equation 2. uR are taken from ref 1, with the exception of up for OMe (0.28) and N(CH& (0.19). These values are those suggested by Charton" as being more suitable for aqueous solution data.
6AGog for a large number of gas-phase proton exchange processes, including reaction 1are quite precisely described by eq 2. (2) 6AGog = Paba + P F ~ F+ P R ~ R
There is a large body of evidence suggesting that polarizability effects on proton-exchange reactions in aqueous solutions are very small, whenever efficient charge dispersal by the solvent can take p l a ~ e . ' ~ ~Thus, J ~ (6AGO - paua) seems a more appropriate quantity for AGO,, t o k e compared to (see Figure 2). I t is clear that with some exceptions, these quantities are linearly related. The correlation covers their full range of variation: 32 and 15 kcal-mol-l. A statistical analysis of the separate regressions generated by the ortho, meta, and para derivatives, shows that they can be embodied into a single equation (eq 3), with n (number of data points) (6AGo, - paua) = -(0.49 f 0.46) + (2.27 f 0.15)6AG0,, (3) = 37, r2 (correlation coefficient) = 0.964, and a standard deviation of 1.3 kcal-mol-'. (pa values are given in Table 11)* The departures from the correlation of the 2-OMe, 3OMe-, 4-OMe, and 3-NMe2derivatives can be understood in terms of differential (i.e., pertaining to both X-Py and X-PyH+) solvation effects involving the methoxy and the N,N-dimethylamino groups. These points, as well as those corresponding to the 2-fluoro- and 2-chloropyridineshave been excluded from the data set leading to eq 3. Two important conclusions can be drawn from this equation: (1) The main difference between gas-phase and solution basicities of pyridines can be quantitatively described by the loss of polarizability stabilization in aqueous solution, as shown by the following analysis: The 6AGog and 6AGo, data for 2-, 3-, and 4-substituted pyridines have been treated by means of eq 2. The corresponding pa, pF, and pR values for 6AGog are given in Table 11. The analysis of 6AGo,, leads to 6AGo,, = (0.6 f 0.8) (0.7 f 1 . 0 ) ~~ (14.6 f 2 . 0 ) ~~ (6.9 f 2.0)CR (4)
+
with n = 14 (excluding 2-F and 2-OCH3),r2 = 0.960, and sd = 0.7 kcabmol-' for 2-substituted pyridines, 6AGo,, = -(0.1 f 0.5) + (0.06 f 0 . 8 6 ) ~-~ (9.1 f 0 . 8 ) ~- ~(5.1 f 0 . 8 ) ~(5) ~ with n = 13, r2 = 0.989, and sd = 0.4 kcal-mol-l for 3substituted pyridines, and 6AG0,, = (0.18 f 0.56) (0.49 f 0 . 6 8 ) ~- ~ (8.2 f 0.3)~F- (12.0 f 0.7)~R(6)
+
(8)(a) Taagepera, M.; Henderson, W. G.; Brownlee, R. T. C.; Beauchamp, J. L.; Holtz, D.; Taft,R. W. J. Am. Chem. SOC.1972, 94, 1369. (b) Aue, D. H.; Webb, H. M.; Bowers, M. T.;Liotta, C. L.; Alexander, C. J.; Hopkina, H. P., Jr. J . Am. Chem. SOC.1976,98,854. (9) Amett, E. M. In "ProtonTransfer Reactions";Caldin, E. F., Gold, V., Eds.; Chapman and Hall: London, 1972; Chapter 3. (10) Taft, R. W. In Roton Transfer Reactions; Caldin, E. D., Gold, V., Ma.; Chapman and Hak London, 1972; Chapter 2.
with n = 13 (excluding 4-OMe), r2 = 0.996, and sd = 0.3 kcal-mol-' for 4-substituted pyridines. In all cases, the pa's are small and the corresponding uncertainties are comparatively quite large. A statistical study of eq 4-6 indicates that ua has indeed little statistical significance. Thus, it is possible to treat the corresponding data sets as functions of UF to UR only. This leads to eq 4/43'. Also notice that in all cases the independent terms are essentially nil within the limits of error. 6AGo,, = (0.18 f 0.56) - (14.3 f 2 . 0 ) ~- ~(7.0 f 2 . 1 ) ~ ~ (4') with n = 14, r2 = 0.952, and sd = 0.7 kcal-mol-' 6AGo,, = ~ ( 0 . 1 3f 0.40) - (9.1 f 1.O)CF - (5.1 f 1.O)CR (5') with n = 13, r2 = 0.988, and sd = 0.4 kcal-mol-' 6AGo,, = -(O.O f 0.4) - (8.2 f 0 . 6 ) ~- ~(12.0 f 0 . 7 ) ~ R (6') with n = 13, r2 = 0.996, and sd = 0.3 kcal.mo1-' These expressions are to be preferred to eq 4-6 for their goodness of fit is essentially the same but have one less adjustable parameter. An attenuation factor, AF is defined as being equal to the rat0 p,(g)/p (aq) for each of the electronic factors, Y (Y = a,F,and Rj. The various AF,'s are collected in Table 11. We observe that AFF and AFR are largest in the meta and para positions, as it can be expected from essentially electrostatic effects. The slope of the line defined by eq 3,2.3 is a measure of the average attenuation of field and resonance effects in aqueous solution. In the case of anilines, the attenuation factor is 4.211 while for phenols, it reaches 6.8.l2?l3 This is reasonable, because anilinium ions can disperse charge through three hydrogens bonds, while only one is available to pyridinium ions. It is also known that bulk water is a strong hydrogen bonding acid,14but it is a rather weak base,14so that charge dispersal from phenoxides is more important. (2) All 2-mono- and 2,S-diaUryl pyridines are close to the line defined by eq 3. This is remarkable because (a) polarizability effects for these compounds are often very large in the gas-phase, and (b) it implies the absence of major steric effects on solvation of the pyridinium ion center. The essentially "normal" behavior of 2,6-di-tert-butylpyridine (DTBP) is important, for it indicates that charge dispersal through hydrogen-bonding is present in aqueous DTBPH+. On the basis of other results, le Noble,15 Hopkins,sJe A u ~and , ~ Meot-Nerd and their co-workers have come to (11) Lau, Y. K.; Nishizawa, K.; Tse, A.; Brown, R. S.;Kebarle, P. J. Am. Chem. SOC.1981,103,629. (12) McMahon, T. B.; Kebarle, P. J. Am. Chem. SOC.1977,99,2222. (13) Mishima, M.; McIver, R. T., Jr.; Taft, R. W.; Bordwell, F. G.; Olmstead, W. N. J . Am. Chem. SOC.1984,106,2717. (14) Kamlet, M. J.; Abboud, J. L. M.; Abraham, M. H.; Taft, R. W. J . Og. Chem. 1983,48, 2877. (15) Le Noble, W. J.; Asano, T.J . Org. Chem. 1975, 40, 1179. (16) Hopkins, H. P., Jr.; Ali, S. Z. J.Phys. Chem. 1980,84,203,2814.
J. Org. Chem. 1988,53, 1140-1146
1140
I;
gaseous 2,6-DTBPH+ suffers a loss of entropy of ca. 6 calsmol-l-K-l because of hindered rotations of and within the tert-butyl groups, while Meot-Ner4 estimates the entropy loss of aqueous 2,6-DIPPH+ to be small. Thus, a difference of free energy of 1.7 kcal-mol-l can be well accounted for by this entropic effect. We last notice that eq 3 assumes a constant attenuation factor for resonance and field effects in the ortho, meta, and para positions. As shown in Table 11, this is only an approximation. Using eq 2 and keeping in mind that p,(aq) = 0, eq 7 obtains.
-
c
12.0
Y
6AGog - P = &AGOaq-t [pF(g)aF(g)- p~(aq)&q)] + [pR(g)'JR(g)- p ~ ( a q ) d a q ) l(7)
-3.0
-8.0
kcal-mol- 1
This equation is represented in Figure 3, wherein the line drawn is the theoretical one (zero intercept and unity slope).18 Notice that for all substituents with the exception of NMe, and OMe" we have taken q ( g ) = aF(aq) and aR(g) = aR(aq). It is of interest that the points corresponding to the 2-fluoro- and 2-chloropyridines are now close to the theoretical line. On the other hand the amino, N,N-dimethylamino, and methoxy derivatives often show significant departures from the behavior predicted by eq 7. This result strongly supports the concept that these departures originate in specific solvent-solute interactions involving the substituents.
Acknowledgment. We would like to thank the Comit4 6A Giaq)t[PF(g)u~OI-PF(Oq)~(aq~~~g)u~g)-~(~q)u~ Conjcnto Hispano-Norteamericano para la Cooperacidn, -18.0 I I 1 I Cientifica y TBcnica for a grant (CCB 84-02-045). -18D -8.0 on 2.0 12.0 Registry No. Pyridine, 110-86-1;pyridinium ion, 16969-45-2. ortho; (0)meta; ( 0 )para. Figure 3. Plot of eq 7: (0) the same conclusions. Furthermore, should polarizability effects be the only difference between gas-phase and solution basicities of pyridines, then 6AGo, values for 2,6DTBP and 2,6-diisopropylpyridine (2,6-DbP) should be quite close. In fact, they differ by 1.7 kcalsmol-l, the latter being more basic. Hopkins and Aue6 have concluded that
(17) Charton, M. R o g . Phys. Org. Chem. 1981,13, 119. (18) The actual correlation equation has an intercept of 0.41 f 0.57 kcalsmol-' and a slope of 1.01 k 0.07, with n = 39 (all the available data), r2 = 0.955, and sd = 1.6 kcal-mol-'. Excluding the data for the 2-OMe, 3-OMe, and 3-NH2derivatives, the intercept and slope become, respectively, equal to 0.45 f 0.36 kcal.mol'* and 1.03 f 0.05, with n = 36, 9 = 0.987. ad = 1.0 kcalmmol-'.
Alkylation of Allylic Derivatives. 13. Cross-Coupling Reactions of the Isomeric 2,3,4,4a,5,6-Hexahydro-%-naphthalenyl Carboxylates with Organocopper and Grignard Reagents Ted L. Underiner and Harlan L. Goering* Samuel M.McElvain Laboratories of Organic Chemistry, Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706
Received August 19, 1987 The regio- and stereochemistry of cross-coupling of cis- and trans-2,3,4,4a,5,6-hexahydro-2-naphthaJenyl pivalate (1-OPiv)with organocopper and Grignard reagents has been investigated. Alkylation of cis- and trans-1-0Piv (2) primarily with LiCuMezand LiCuBuzgives the conjugated product 2,3,4,4a,5,6-hexahydro-2-alkylnaphthalene via a-anti-alkylation. Alkylation of cis- and trans-1-OPiv with LiCu(CN)Me and LiCu(CN)Bugives both 2 and 3,4,4a,5,6,8a-hexahydro-8a-alkylnaphthalene (3). In this case, 2 arises nearly equally from a- and c-alkylation. Alkylation of cis- and trans-1-0Piv with LiCuPhzand LiCu(CN)Ph gives only 2 as a result of a-anti-alkylation. Cross-coupling of cis- and trans-1-0Piv with Grignard reagents occurs remarkably fast. Reaction of cis- and trans-1-0Piv with Grignard reagents gives identical product mixtures. Evidence for the intermediacy of radical intermediates and mechanistic implications are discussed. We have extended our initial studies' of the regio- and stereochemistry of alkylation of the cis- and trans2,3,4,4a,5,6-hexahydre2-naphthalenyl system with organocopper reagents. This paper reports an investigation of (1) Underiner, T. L.; Goering, H. L. J. Org. Chem. 1987, 52, 897.
the regie and stereochemistryof alkylation of the epimeric pivalates (trans-1-OPiv and cis-1-OPiv) with LiCuR, and LiCu(CN)R in which the alkyl groups are methyl and n-butyl and with LiCuPh, and LiCu(CN)Ph. The unexpected proclivity of this system to couple with Grignard reagents in the absence of cuprous salts precluded a study of the copper(1)-catalyzed cross-coupling of 1-OPiv with
0022-3263/88/1953-1140$01.50/00 1988 American Chemical Society
